Titrated Insulin Glargine Research Articles

Characteristics associated with maintenance of mean A1C

OBJECTIVE: To assess the success and baseline predictors of maintaining glycemic control for up to 5 years of therapy using basal insulin glargine or standard glycemic care in people with dysglycemia treated with zero or one oral glucose-lowering agents. RESEARCH DESIGN AND METHODS: Data from 12,537 participants in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were examined by baseline glycemic status (with or without type 2 diabetes) and by therapeutic approach (titrated insulin glargine or standard therapy) using an intention-to-treat analysis. Median values for fasting plasma glucose (FPG) and A1C and percentages with A1C<6.5% (48 mmol/mol) during randomized treatment were calculated. Factors independently associated with maintaining updated mean A1C<6.5% were analyzed with linear regression models. RESULTS: Median A1C in the whole population was 6.4% at baseline; at 5 years, it was 6.2% with glargine treatment and 6.5% with standard care. Of those with diabetes at baseline, 60% using glargine and 45% using standard care had A1C<6.5% at 5 years. Lack of diabetes and lower baseline A1C were independently associated with 5-year mean A1C<6.5%. Maintaining mean A1C<6.5% was more likely with glargine (odds ratio [OR] 2.98 [95% CI 2.67-3.32], P<0.001) than standard care after adjustment for other independent predictors. CONCLUSIONS: Systematic intervention with basal insulin glargine or standard care early in the natural history of dysglycemia can maintain glycemic control near baseline levels for at least 5 years, whether diabetes is present at baseline or not. Keeping mean A1C<6.5% is more likely in people with lower baseline A1C and with the glargine-based regimen.

Contributions of Basal and Postprandial Hyperglycemia Over a Wide Range of A1C Levels Before and After Treatment Intensification in Type 2 Diabetes

OBJECTIVETo determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A1c (A1C) >7.0% while on prior oral therapy.RESEARCH DESIGN AND METHODSSelf-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents). Hyperglycemic exposure (>100 mg/dL [5.6 mmol/L]) as a result of BHG versus PPHG was calculated.RESULTSOn prior oral therapy, 1,699 participants (mean age 59 years, diabetes duration 9 years) had mean fasting plasma glucose (FPG) of 194 mg/dL (10.8 mmol/L), and mean A1C was 8.7%. BHG contributed an average of 76–80% to hyperglycemia over the observed range of baseline A1C levels. Adding basal insulin for 24 or 28 weeks lowered mean FPG to 117 mg/dL (6.5 mmol/L), A1C to 7.0%, and BHG contribution to 32–41%. Alternative regimens reduced FPG to 146 mg/dL (8.1 mmol/L), A1C to 7.1%, and the contribution of BHG to 64–71%. BHG contributions for patients with A1C averaging 7.6–7.7% were 76% at baseline and 34 and 68% after adding basal insulin or other therapies, respectively.CONCLUSIONSWhen A1C is >7.0% despite oral therapy, BHG routinely dominates exposure. Intensified therapy reduces A1C and changes this relationship, but BHG amenable to further intervention still accounts for one-third of total hyperglycemia after basal insulin treatment and two-thirds after alternative methods.

Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month ‘proof-of-concept' study

AimStepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated.MethodsThis was a 6-month, parallel-group, randomized, open-label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA1c 7.5–9.5%) using any basal insulin underwent a 3-month run-in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA1c >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2-h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre-meal/bedtime BG 100–120 mg/dl (5.5–6.7 mmol/l; US).ResultsHbA1c and fasting plasma glucose levels decreased during the run-in period. In the 3 months after randomization, more participants in the basal-plus-bolus group reached HbA1c <7.0% than the basal-only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA1c (−0.37 vs. −0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups.ConclusionsIn people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects.

How Basal Insulin Analogs Have Changed Diabetes Care

How Basal Insulin Analogs Have Changed Diabetes Care

Titration of Insulin Glargine in Patients with Type 2 Diabetes Mellitus in Asia: Physician- Versus Patient-Led? Rationale of the Asian Treat to Target Lantus Study (ATLAS)

the AT-LANTUS Study demonstrated that a simple subject-administered titration algorithm significantly improved glycemic control with a low incidence of severe hypoglycemia compared with a physician-managed titration. However, in the AT-LANTUS Study Asian patients were under-represented, and more than 70% of the patients were already treated with insulin. The Asian Treat to Target Lantus Study (ATLAS) will compare the effectiveness of a patient- versus physician-led initiation of insulin glargine-based basal management in the specific setting of Asia and Russia (as is routinely used in Western countries). This report presents the study design of ATLAS. subjects are 40-75 years old (body mass index ≥ 20 and ≤ 40 kg/m(2)) with type 2 diabetes mellitus (T2DM) of >2 years in duration, suboptimally controlled (hemoglobin A1c [HbA1c] ≥ 7.0% and ≤ 11%) with stable doses of two oral antidiabetes drugs (OADs) (sulfonylureas, biguanides, α-glucosidase inhibitors, dipeptidyl peptidase-IV inhibitors, and glinides) for more than 3 months, and not using insulin. The subjects will be randomized to either the patient-led or the physician-led titration arm, where the insulin dose will be adjusted to achieve a target fasting plasma glucose (FPG) value of 110 mg/dL (6.1 mmol/L). the primary outcome will be change in mean HbA1c at 6 months from baseline. The analysis plan prespecifies a hierarchical testing procedure for the primary outcome. If noninferiority is achieved using a 0.3% HbA1c boundary, we will go on to undertake a test for superiority. Secondary outcomes will also include number of patients reaching American Diabetes Association target HbA1c with or without hypoglycemia and analysis of FPG profiles in the two groups. ATLAS will provide information on the relative safety and efficacy of a patient- versus physician-led titration strategy for insulin glargine-based basal insulin initiation in patients who are not controlled with two OADs in Asia and Russia. The results of the study may guide policymakers to translate data into clinical practice.

Effect of insulin glargine on glycaemic control and weight in obese and non‐obese people with type 2 diabetes: data from the AT.LANTUS trial

To explore glucose lowering response to insulin initiation or switch to insulin glargine in obese and non-obese individuals with type 2 diabetes mellitus (T2DM) and to examine weight gain and hypoglycaemic episodes in this group. Post hoc subgroup analysis using data of obese and non-obese participants from a large multi-centre (4555 participants with T2DM), multi-national 24-week randomized controlled trial of investigator titrated insulin glargine versus patient self-managed titrated insulin glargine. This analysis was carried out to compare two subgroups: obese (> or =30 kg/m2) and non-obese (<30 kg/m2) participants. The mean body mass index (BMI) values were 33.7 kg/m2(n = 1833) and 25.9 kg/m(2)(n = 2755) in obese and non-obese subjects, respectively. There was a significant reduction in glycated haemoglobin (HbA1c) from baseline in both subgroups but no significant difference between subgroups (1.15 vs. 1.15%, p = 0.50). Overall, there was a 1.21 kg (s.d. 3.3) increase in weight in individuals who were non-obese and a 1.08 kg (s.d. 3.9) increase in obese individuals (p = 0.67). There was no significant difference in the proportion of participants achieving an HbA1c of <7.0% at 6 months in both the subgroups (28.8 vs. 27.1%, p = 0.20). In multiple logistic regression, BMI was not a prognostic factor in achieving a target of HbA1c < or = 7.0%. There was no significant difference in severe hypoglycaemic episodes between obese and non-obese subgroups (1.3 vs. 1.0%); however, significantly more non-obese individuals experienced nocturnal hypoglycaemic episodes(4.5 vs. 2.4%, p < 0.05). In this study, treatment with insulin glargine in people with T2DM was associated with a significant reduction in HbA1c without differential increase in weight gain in obese and non-obese subgroups. Rates of severe hypoglycaemia were not different between obese and non-obese subgroups.

Optimierung der glykämischen Kontrolle und Dosistitration mit Insulin Glargine (Lantus®) durch frei praktizierende Ärzte in der Schweiz: Resultate des OPTI-LAN Praxiserfahrungsberichtes

National and international societies have published guidelines regarding glycaemic control in type-2 diabetes mellitus. Clinical studies have shown that glycaemic control of type-2 diabetes mellitus can be improved using simple algorithms for titration of insulin Glargine (Lantus). It is unclear, to what degree published guidelines are adopted in daily practice in Switzerland. We performed a postmarketing study on the adoption of published guidelines regarding glycaemic control and the use of algorithms for titration of insulin Glargine doses by 77 general practitioners in Switzerland. Data collection was done prospectively over 6 months from September 2005 to September 2007. A total of 317 patients were included with a mean age of 63 +/- 11 years, 137 (43%) were female and 298 (94%) had type-2 diabetes. Average diabetes duration was 8 +/- 6 years. The initial average HbA1C and fasting plasma glucose were 8.9 +/- 1.6% and 10.1 +/- 3.2 mmol/l respectively. This, despite treatment with at least one oral hypoglycaemic agent (83% of patients) and/or insulin (47% of patients). As target the treating physicians chose an HbA1C < or = 7% for 284 patients (90%) and a fasting plasma glucose < or = 7 mmol/l for 245 patients (77%); thresholds that correspond to the guidelines of the Swiss Society of Endocrinology and Diabetes (SSED). The algorithm developed Riddle et al. was used by 33% of treating physicians; whereas 17% of physicians used a schedule proposed by the American Diabetes Association (ADA) and by the European Association for the Study of Diabetes (EASD) that is generally adapted by the patients themselves. During the 6-month treatment with insulin Glargine (Lantus) 196 patients (62%) achieved the SSED guidelines for glycaemic control. On average HbA1C was reduced by 2.1% (8.9 vs. 6.8%) and fasting plasma glucose by 3 mmol/l (10.1 vs. 7.1 mmol/l). On average insulin dose was increased by 14 IU (from 16 to 30 IU). Overall 91% of patients were satisfied with the way insulin doses were adapted. In 64% general wellbeing improved during the treatment period and in 27% it was unchanged. In daily practise in Switzerland the recommendations of the SSED are implemented to a high degree. Using insulin Glargine (Lantus) recommended goals of glycaemia can be rapidly and adequately achieved and patient satisfaction can be improved.

One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial.

OBJECTIVETraditional blood glucose–lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in β-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp–derived measures of β-cell function, glycemic control, and body weight.RESEARCH DESIGN AND METHODSSixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety.RESULTSTreatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09–2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: −0.8 ± 0.1 and −0.7 ± 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference −4.6 kg, P < 0.0001). β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy.CONCLUSIONSExenatide significantly improves β-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, β-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.

Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: A multinational, randomized, open-label, two-period, crossover noninferiority trial

Objective: This study was conducted to compare the efficacy and safety profiles of exenatide and insulin glargine therapy in patients with type 2 diabetes who had not achieved glucose control with metformin or sulfonylurea monotherapy. Methods: This multinational, randomized, open-label, crossover noninferiority study compared the efficacy of exenatide 10 pg BID and insulin glargine QD (titrated targeting a fasting serum glucose (FSG) level ≤5.6 mmol/L) in patients with type 2 diabetes treated with a single oral antidiabetic agent. The study included two 16-week treatment periods. The primary a priori outcome variable was the change in glycosylated hemoglobin (HbA l c ). Secondary outcomes included the proportion of patients achieving the American Diabetes Association (ADA) target HbA l c of ≤7% and the European Association for the Study of Diabetes target of ≤6.5%, the change in FSG, end-point values and change in the 7-point self-monitored glucose profile, and change in body weight. Adverse events were assessed based on standard laboratory tests and patient reports. Results: One hundred thirty-eight patients were randomized to study treatment (52.9% female, 47.1% male; 79.7% white; mean [SEM] age, 54.9 [0.8] years; duration of diabetes, 7.4 [0.4] years; body mass index, 31.1 [0.4] kg/m 2; weight, 84.8 [1.4] kg) while continuing to receive metformin (55.1%) or a sulfonylurea (44.9%). The population had a baseline least squares (LS) mean (SEM) HbA l c of 8.95% (0.09%) and an LS mean FSG concentration of 12.0 (0.3) mmol/L. Both exenatide and titrated insulin glargine therapy were associated with similar significant changes from baseline in HbA 1c (both, -1.36% [0.09%]; P < 0.001); the difference between groups was not statistically significant. The LS mean HbA 1c at end point was above the ADA target with both treatments (exenatide, 7.57% [0.09%]; insulin glargine, 7.58% [0.09%]). Similar proportions of patients achieved an HbA 1c ≤7% (37.5% and 39.8%, respectively; P = NS) or ≤6.5% (21.5% and 13.6%). Patients lost weight during exenatide treatment, whereas they gained weight during insulin glargine treatment; the between-group difference in weight change was statistically significant (LS mean difference, -2.2 [0.3] kg; 95% CI, -2.8 to-1.7; P < 0.001). Both exenatide and insulin glargine were associated with significant reductions from baseline in FSG (-2.9 [0.2] and -4.1 [0.2] mmol/L, respectively; both, P < 0.001), although the reduction was significantly greater with insulin glargine compared with exenatide (LS mean difference, 1.2 [0.3] mmol/L; 95% CI, 0.7 to 1.7; P < 0.001). Compared with insulin glargine, exenatide was associated with significantly lower 2-hour postprandial glucose (PPG) excursions ( P < 0.016) and total daily mean glucose excursion ( P < 0.001). The proportions of patients reporting nausea during exenatide and insulin glargine treatment were 42.6% and 3.1%, respectively; the proportions reporting vomiting were 9.6% and 3.1%. The incidence of hypoglycemia in the 2 groups was 14.7% and 25.2% ( P = NS). Condusions: In this open-label, crossover study, treatment with exenatide or insulin glargine for 16 weeks was associated with similar significant improvements from baseline in HbA 1c, independent of treatment order. The improvements in HbA 1c from baseline did not differ significantly between treatment groups. Exenatide therapy was associated with significant reductions in body weight and PPG excursions compared with insulin glargine, whereas insulin glargine was associated with a significantly greater reduction in FSG compared with exenatide. These findings provide additional information to guide treatment decisions in patients with type 2 diabetes who are potential candidates for either therapy. ( Clin Ther. 2007;29:2333-2348) Copyright © 2007 Excerpta Medica, Inc.

Improving metabolic control in sub-optimally controlled subjects with Type 1 diabetes: Comparison of two treatment algorithms using insulin glargine

This study assessed the incidence of severe hypoglycaemia with two insulin glargine titration algorithms: Algorithm 1 (increments of at least 10%, but not exceeding 4 U) versus Algorithm 2 (1–6 U increments). In this multicenter ( n = 409), multinational ( n = 54), open-label, 24-week randomized trial in 2442 subjects with sub-optimally controlled Type 1 diabetes (T1DM), mean prior insulin therapy duration was 14.6 ± 10.3 years. The incidence of severe hypoglycaemia was similar with Algorithms 1 and 2 (16.6 events/100 patient–years versus 14.4 events/100 patient–years). There were similar rates of both symptomatic and nocturnal hypoglycaemia. HbA 1c and fasting blood glucose (FBG) decreased significantly (baseline to endpoint; p < 0.001), and comparably with Algorithms 1 and 2 (HbA 1c: −0.64% versus −0.72%; FBG: −57 mg/dL versus −59 mg/dL). Mean basal insulin dose increased with both algorithms (+5.7 U versus +5.9 U). In a diverse population with longstanding T1DM, transfer from any insulin regimen, including basal–bolus or premixed insulin to an insulin glargine-based regimen resulted in significant improvements in glycaemic control, with low rates of severe hypoglycaemia, irrespective of the titration algorithm used.

Renal Status Among Patients Using Metformin in a Primary Care Setting

Metformin use has been associated with lactic acidosis, a rare but potentially lethal condition characterized by elevated blood lactate levels (>5 mmol/l), an increased lactate-to-pyruvate ratio, and an increased anion gap (1). Most cases of metformin-associated lactic acidosis occur in patients with preexisting conditions (e.g., renal insufficiency, hepatic impairment, or heart failure) (2). When used as labeled, metformin may not increase the risk of lactic acidosis beyond what already exists with such conditions (3–5). However, despite evidence suggesting that the risk of lactic acidosis may be reduced if metformin is avoided in patients with renal impairment, and despite the ready availability of serum creatinine tests to assess renal function, inappropriate prescribing of metformin is a concern (2,3,6–9). The randomized, open-label Glycemic Optimization with Algorithms and Labs At Po1nt of Care (GOAL A1C) study was designed to evaluate the impact of point-of-care versus laboratory testing of glycosylated hemoglobin (A1C) and monitored versus standard titration of insulin glargine on glycemic control in patients with type 2 diabetes inadequately controlled on oral agents. This study also provided an opportunity to assess appropriateness of metformin therapy based on serum creatinine levels at enrollment in a large, predominantly primary care population. This assessment forms the basis of …